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an Economist Intelligence Unit business healthcare

Ultra Orphan Drugs


National Commissioning Group



It is known that guidelines based on similar research evidence can produce recommendations that vary considerably between countries. One of the reasons why this is the case is that there are differences in local priorities and in the underlying factors that drive them, including the different health systems that can operate between and within countries.

Ultra-orphan is the term given to drugs that are used to treat extremely rare diseases that are chronically debilitating or life-threatening. Ultra-orphan drugs are often expensive on a per patient basis because patient numbers, and therefore the number of sales, are so low, and consequently, these drugs can have a disproportionately large effect on regional commissioning budgets. The extent to which guidance regarding the use of ultra-orphan drugs varied internationally was unknown, and the degree to which prescribers followed such guidance, uncertain. In addition, examples exist where local or regional funding arrangements take precedence over national protocols. These local variations within countries had not hitherto been documented comprehensively. Yet understanding these policies and variations is of vital importance in that helps to ensure that national policy guidance, which will have large clinical and cost consequences, is informed by experiences in other parts of the world.


The problem

The cost to the NHS of the drugs used to treat lysosomal storage disorders - enzyme replacement therapy (ERT) and substrate reduction therapies (SRT) - is substantial and increasing. The birth frequency of all such disorders is approximately 1 in 7,000 births. There are also new, innovative drugs used in clinical trials, but which are not yet licensed. The National Commissioning Group monitor the ultra orphan drugs budget, and ensure that treatment is in accordance with agreed clinical guidelines.

Bazian was commissioned to conduct a review of current advice and practice in the use of a selection of ultra-orphan drugs currently licensed to treat lysosomal storage disorders. The conditions and drugs to be assessed were (ERT= enzyme replacement therapy; SRT= substrate reduction therapy):

  • Gaucher disease. ERT: imiglucerase (Cerezyme; Genzyme Corp); SRT: miglustat (Zavesca; Actelion Pharma)
  • Fabry disease. ERT: agalsidase beta (Fabrazyme; Genzyme Corp); agalsidase alpha (Replagal; Shire)
  • MPS I. ERT: laronidase (Aldurazyme; Genzyme Corp)
  • MPS II. ERT: idursulfase (Elaprase; Shire)
  • MPS VI. ERT: galsulfase (Naglazyme; BioMarin)
  • Pompe disease. ERT: alglucosidase alfa (Myozyme; Genzyme Corp)
  • Niemann-Pick disease type C. SRT: miglustat (Zavesca; Actelion)

It was hoped that comparing and contrasting the policies in different countries and reviewing the actual application of those policies in different health systems would give a deeper understanding of current practice, around which more realistic and effective guidelines could be constructed.


Our solution

Bazian used systematic searching methods to identify guidelines and protocols in a selection of OECD countries with similar per capita national expenditure on health as the UK.   We searched a comprehensive range of guidelines and research databases, supplemented this with a grey literature search and email communication with international researchers and clinical experts in the area. In addition to the search and appraisal, an online survey was sent out to patient group contacts, asking about actual day to day use of the drugs.

We found that published guidelines and protocols describing treatment with ultra-orphan drugs were broadly similar and based around the indications for treatment found in the marketing approval of relevant medicines regulatory bodies.  Two countries (Australia and New Zealand) produced national guidance that was more restrictive than the licensed indications and explicitly do not fund the drugs routinely on cost effectiveness grounds. Regional variations to a national funding agreement were reported from Canada; where no national guidelines or protocols exist it was found that patient groups were active in securing access to these drugs for individual patients; application to the manufacturer for ‘compassionate use’ on a named patient basis was frequently quoted.


The outcome

The project report is available here. It has helped UK national commissioners to better manage the cost effective use of ultra orphan drugs for lysosomal storage disorders, and further understand the mechanisms of day-to-day management in Europe, the Americas and Australasia.


 “Bazian provided the national commissioning team with an analysis of policies used in various countries for the use of a set of very expensive drugs - enzyme replacement therapies for lysosomal storage disorders. The project was initiated to establish whether our policies were in line with international practice. Bazian understood the brief very well and delivered an excellent report in both quality and relevance. Project updates were appropriate and to the point. Bazian services were of an excellent quality and I would be happy to make use of their services again”

Dr Edmund Jessop, Medical Advisor National Commissioning Group